Prostate cancer

WHAT IS IT?

Prostate cancer, unlike other types of cancer, evolves very slowly. On average it takes about 10-15 years to progress and put the life of the man who suffers from it at risk. This fact means that, although it is very prevalent, it is not the leading cause of death in men, bearing in mind that the life expectancy of a man in Spain is 80 years.

In order to design an individualized and personalized therapy that meets the needs of each patient, a global assessment of the man’s health, his age and the aggressiveness of his cancer is essential. We should not offer patients “the solution I have” but the best solution for each of them.

SYMPTOMS

Prostate cancer does not usually produce symptoms. Most of the time it is diagnosed before it has any effect.

The symptoms or manifestations that a man with prostate cancer usually presents are secondary to benign prostatic hyperplasia, which usually coexists in the same: difficulty urinating, loose urine stream, high frequency of urination, urinating at night, etc.

When prostate cancer is very advanced it can cause local symptoms: bleeding in the urine, great difficulty urinating, perineal pain and, on occasions, it can invade the rectum and cause digestive symptoms.

In cases of cancer dissemination, bone pain, back pain, pathological bone fractures may appear and, depending on the organ in which they are located, they may produce one symptomatology or another.

DIAGNOSIS

Although prostate cancer evolves very slowly and symptoms appear when the disease is very advanced, it is a type of cancer that can be diagnosed early.

PROSTATE CANCER SCREENING

Screening for prostate cancer is first performed by digital examination (digital rectal examination) and is complemented by a blood test to measure PSA (prostate specific antigen). Nowadays we have diagnostic tests that allow us to detect the disease before the symptoms appear: pro-PSA, 4kallikreins, PCA-3, MDX and others.

When we find an elevated PSA or a suspicious rectal examination, we will indicate the performance of a magnetic resonance imaging (MRI) or microultrasound to see if there are suspicious lesions of prostate cancer. Today, thanks to MRI we are able to see prostate cancer. Before the advent of MRI and ultrasound we were not.

After a general physical examination, your physician will ask you a few questions about your symptoms and medical history and perform one of the following tests:

• Digital rectal exam (digital rectal exam): This is a test in which the doctor inserts a finger into the patient’s rectum to detect the existence of any hard irregular area in the prostate (swelling or lump), which could be a sign of cancer.
• Blood test: This is a very useful test to detect what are known as “silent cancers”. It is also called the prostate-specific antigen (PSA) test. It consists of drawing blood in order to measure the level of PSA, a protein produced by the prostate.
• Urine test: A urine sample is taken to determine if there are any hematuria or abnormalities. It could indicate the presence of an infection, prostate hyperplasia or cancer markers.
• Transrectal ultrasound (TRUS): consists of the use of sound waves to create an image of the prostate in order to detect small tumors. A probe is placed in the patient’s rectum for 10 to 20 minutes. This test makes it possible to evaluate the shape and size of the prostate, in addition to assisting in taking biopsies. Its performance in detecting tumor by image is low.
• Magnetic Resonance Imaging: with MRI we are able to detect suspicious areas of tumor. According to the changes identified in it, they are classified as PIRADS 1-5. PIRADS 4 and 5 are all to be biopsied, the decision for PIRADS 3 will be clinical depending on the clinical characteristics of the patient. PIRADS 1 and 2 have a very low probability of harboring a tumor, therefore they are not biopsied. This technique is very important because it also allows us to visualize only those tumors that are going to be truly dangerous for the patient, that is to say, that are going to have clinical significance or that are going to put the patient’s life at real risk. It will allow us not to biopsy and diagnose those tumors that are indolent or of low risk. Finally, MRI provides us with very useful information on tumor size, prostate size, tumor staging, its exact location in the prostate, if it is located near the capsule, if it invades the seminal vesicles, etc.
• Prostate biopsy: The only way to confirm the diagnosis of prostate cancer is by taking a tissue sample (biopsy). The biopsy consists of inserting a needle into the prostate with the intention of extracting part of its cellular tissue and analyzing it. This analysis makes it possible to confirm or rule out the existence of the disease.

FUSION BIOPSY

Classically, the diagnosis of prostate cancer (PC) has been based on the determination of the PSA value in blood and palpation of the prostate through the rectum. When one of these two parameters was abnormal, a randomized prostate biopsy was performed with an ultrasound scanner (ECHO), which is an imaging test that provides very poor visualization of the prostate and only serves to direct the punctures to the gland, and a minimum of 8-10 fragments of prostate tissue were taken randomly via the transrectal route. This clinical practice, although widespread throughout the world, has led to overdiagnosis and overtreatment of patients. Patients with very unaggressive tumors, which, left to their natural evolution, would not put the patient’s life at risk, were treated. For this reason, PSA has been questioned as a screening test for the diagnosis of prostate cancer, which has been banned in the USA.

This is the reason that has led us to change our diagnostic approach. When a clinical situation of suspected prostate cancer occurs, we perform magnetic resonance imaging (MRI). This imaging test, when MRI of a minimum of 1.5 teslas and a trained radiologist are available (fundamental factors), gives us very precise information. With this technique, suspicious areas of prostate cancer can be visualized, which are marked by the radiologist.

It has been shown that these areas that are seen in MRI -and not with other imaging tests- are, in general, prostate cancer that will be clinically significant. At the same time, it has been proven that the tumors that are not detected are usually of very low grade and do not put our patients’ lives at risk. Therefore, a good MRI interpreted by an expert Uro-radiologist has become the cornerstone for the diagnosis of prostate cancer.

The MRI marked with the tumor area provides us with the possibility of performing a fusion biopsy. This procedure is performed in the operating room with a special Ultrasound (ECHO) and fuses the MRI image with the ECHO image. We are now able to perform a biopsy of the areas that are really suspicious for prostate cancer. This test is performed transperineally, making it possible to biopsy the anterior aspect of the prostate, which previously, with the transrectal approach, was not feasible.

With this technique we know exactly what tumor we have, how far it reaches and its degree of aggressiveness in order to be able to design a personalized treatment for each patient. It has also opened the door for us to be able to perform focal therapy, with which we treat only the tumorous area of the prostate, leaving the rest of the gland unharmed. We obtain the same oncological result, that is to say, the same cure, but with minimal side effects.

Advantages of a fusion biopsy:

• More accurate and complete information of your Prostate Cancer.
• Access to biopsy the anterior prostatic face (transrectal impossible).
• We avoid unnecessary biopsies, that is, we avoid overdiagnosis and overtreatment.
• Possibility of Focal Therapy.
• Fewer complications.

FUSION BIOPSY WITH PET

Nevertheless, nowadays we go a step further and we not only seek to improve the information provided by a better image, but we can also perform a PET scan to make a functional assessment of the tumor. A PET is capable of detecting tumors with PSA levels of 1 that we did not even suspect existed before. For this reason, we are pioneers in our country in performing PET fusion biopsies, obtaining the best biopsies that can be performed.

EXACTVU OR MICROULTRASOUND

Microultrasound is a new technology that allows us to replace MRI for the diagnosis of prostate cancer. Thanks to them, we can see tumor lesions that could not be seen with normal ultrasound and can be seen with MRI, thus avoiding the need for the patient to undergo an MRI. In addition, if we detect something during the test, we can perform the biopsy at the same time. This is a very attractive technology that will provide us with greater versatility and operability in the management of prostate cancer without losing reliability compared to MRI.

TREATMENT

In many cases, prostate cancer is treated over a long period of time because it is a type of cancer that develops very slowly. The treatment will depend, above all, on the stage of progression of the disease.

There are different ways of intervening to reduce or remove prostate cancer:

• Active surveillance (AS): since there are tumors that are not aggressive, in selected patients we can not treat and monitor the tumor closely. We will only treat if we detect that the aggressiveness of the cancer is increasing. In order to be able to include patients in VA it is essential to have a solid and strict program in which we really do a very close follow-up with PSA, MRI and prostate biopsies. The advantage is that we only treat the tumor when it looks like it is going to start putting the patient’s life at risk, but we can still treat it without risk. The disadvantage is that many tests have to be performed, some of them invasive, such as prostate biopsies. In general terms it is a good option for patients diagnosed with a low risk tumor: Gleason 3+3 (Gleason 6) in pathological anatomy a maximum of 3 cylinders, PSA less than 10 and clinical stage T1c-T2a.

• Surgery: This procedure consists of the complete removal of the prostate gland and seminal vesicles. In some cases the lymph nodes in the pelvic area are also removed. It can be performed by various approaches: open, laparoscopic or robotic. None of these approaches has been shown to be superior to the others in terms of oncologic control or better preservation of the patient’s voiding or sexual function. However, robotic surgery, such as DaVinci (intuitive surgery) and Hugo (Medtronic), seems to have been shown to improve most surgeons and to have much better results.When performing surgery on a patient it is very important to make an individualized assessment where we consider their specific oncological characteristics without neglecting the voiding and sexual function of each individual. In my team, we carry out an individualized planning and we evaluate all the determining factors. It is mandatory to assess the relationship of the tumor with the prostatic capsule and its location to plan an intrafascial, interdascial or extrafascial surgery to avoid unwanted surgical margins.

• Radiotherapy: is the administration of ionizing radiation for the treatment of cancer. It can be administered alone or combined with surgery. In the case of prostate cancer there is a modality called brachytherapy, in which radioactive seeds are inserted into the prostate gland to administer the treatment. External radiotherapy is done by applying radiation through external machines. Brachytherapy can only be used in patients with low-risk tumors. Radiotetarpy is a good treatment option and is widely used for many tumors.There is a false belief that radiotherapy does not produce side effects or complications, this is not true. The undesirable effects of radiotherapy usually appear over time, starting at 18-24 months. It has been demonstrated that radiotherapy produces sexual dysfunction or impotence and urinary incontinence with the same frequency as surgery. In addition, when intermediate or high risk prostate tumors are irradiated, androgen deprivation or suppression of testosterone (an essential hormone for male sexual life) must be produced, which will cause total sexual dysfunction in 100% of patients.

From my point of view, surgery offers great advantages over radiotherapy:

1. We have the anatomopathological piece, which allows us to know with greater precision what is the tumor that the patient is suffering from.
2. With radiotherapy, the prostate remains in the prostate bed, which means that there may be oscillations in the PSA. However, after surgery it will be 0 and it is easier to follow up.
3. If complications appear in terms of narrowing or stenosis of the urethra, urinary fistulas, urinary incontinence, erectile dysfunction or others, it is easier to treat with surgery.
4. Irradiating before surgery makes surgery much more difficult in case it is necessary later, while it is easier to operate and irradiate afterwards.

On the other hand, radiotherapy also offers some advantages over surgery:

1. there is no exposure to an acute act such as surgery, which can produce complications and bleeding.
2. For high-risk patients it is a less aggressive procedure.

For all these reasons I am usually more in favor of operating before and irradiating later if necessary. Sometimes there are patients that I refer directly to radiotherapy because I consider it more beneficial, because I understand that the tumor is not going to be resectable, or because a patient is at high surgical risk, among other clinical scenarios.

• Hormone therapy: Testosterone – the male sex hormone – is directly related to the evolution of the tumor. Hormonal treatment works to reduce the levels of testosterone in the body or to block its effects on the prostate. By suppressing this hormone in the body, the tumor regresses. Hormone deprivation treatment is usually recommended in association with radiotherapy or when the disease is disseminated in the body.

• Focal therapy: This is used in small, very localized tumors. Only the tumor area is treated, avoiding the possible complications or side effects of other more aggressive therapies.

• Other therapies: there are a multitude of additional and alternative treatments for the treatment of prostate cancer: cryotherapy, HIFU and focal therapy, among others. Most of them should be considered experimental and should be done within a clinical trial.

FOCAL THERAPY

Nowadays, thanks to the excellent information provided by fusion biopsy, we know exactly the extent of the tumor within the prostate, as well as its aggressiveness. This allows us to treat only these index lesions (which ultimately determine the prognosis of the patient’s disease). This is known as Focal Therapy.

Focal therapy allows us to treat only the tumor area, obtaining the same oncologic results, but with minimal functional sequelae. Therefore – unlike radical prostatectomy and radiotherapy – there is no erectile dysfunction, urinary incontinence, urinary fistulas or urethral strictures. The advantages of focal therapy over other prostate cancer treatments are:

• Minimally invasive treatment.
• Minimal side effects on erectile and voiding function. May even improve voiding quality in some patients.
• Minimal risk of bleeding.
• Treatment is outpatient, without hospitalization.
• Short recovery time allows a quick return to daily life.
• Minimal or no pain.
• No need for other secondary treatments such as radiotherapy or chemotherapy.

In order to perform Focal Therapy an optimal energy source is necessary. Each patient must receive a personalized planning and obtain the source that best suits his or her needs. The same energy source does not work for all patients. We have Cryotherapy, HIFU and electroporation:

• Cryotherapy is a minimally invasive treatment that uses very low temperatures to destroy cancer cells. It is used to freeze a specific area of the prostate and destroy all tumor tissue. It is used worldwide and has more than 10 years of clinical experience confirming its safety and effectiveness. Although it is a therapeutic option, I find electroporation and HIFU more attractive.

• High-Intensity Focused Ultrasound (HIFU) is applied transrectally. In just a few seconds, the temperature rises to at least 90o at the focal point, destroying it without affecting other tissues. For this type of therapy, we work with Exablate, a very clean, fast and safe procedure with which we can plan the treatment of a quadrant, half a gland or the entire gland. The oncological and functional results have been very good.

• Electroporation allows maximum preservation of the structures surrounding the prostate gland. The fusion of images from a previous MRI and live ultrasound enables very high precision in the transperineal insertion of three/four very fine needles. A potential difference develops between these needles, which causes short, high-voltage electrical pulses that directly attack the cancer cells. It is a very good source of energy for selected tumors.

In order to have a solid Focal Therapy program, it is necessary to have several of these energy sources. Each one has different indications and will allow us to safely treat our patients with an individualized treatment

ROBOTIC SURGERY

Radical prostatectomy (RP) is a surgical technique consisting of the removal of the prostate and seminal vesicles that has been performed for many years. It began as open surgery, then laparoscopic surgery was introduced in the 1990s and, finally, robotic surgery has been available since the beginning of the 21st century.

No technique per se has been shown to be superior to the others in terms of oncological results and it is not clear in terms of functional results: urinary incontinence and erectile dysfunction. However, it does seem clear that it improves for most surgeons. To perform a perfect radical prostatectomy (RP) it can be done with all three approaches, but it is achieved more often with robotic surgery.

When we are going to operate on a patient we assess him individually beforehand, we look at the size of the prostate, the tumor, the location of the tumor, its relationship with the prostatic capsule, its relationship with the apex and the seminal vesicles and, finally, the functional, voiding and sexual status of the patient. Based on all this, we design a surgical plan that with robotic surgery we are able to comply with 100%, more often than with other approaches. It has also been demonstrated that it seems to have proved to be a less invasive technique with less bleeding, pain, hospitalization, catheterization time, readmission to the emergency room and a faster recovery. For all these reasons, I have become a robotic surgeon.

When a radical prostatectomy (RP) is performed, total removal of the tumor must be achieved, but functional results are also very important. Occasionally, male urinary incontinence or involuntary urine loss may occur. To avoid this, it is advisable to start rehabilitation exercises prior to surgery and to start them early after surgery. In case of urinary incontinence after surgery, it is necessary to treat it in stages with rehabilitation, suburethral mesh implant or even artificial urinary sphincter implant, but it almost always has a solution.

Erectile dysfunction (ED) or impotence is the third area to be evaluated after RP, together with oncological and voiding dysfunction. The results of erectile function are influenced by the state of erection that the patient had prior to surgery, as well as the cardiovascular risk factors he suffers from, the medications he takes, the level of testosterone and others. It is also very important to have a good surgeon who is capable and experienced in the preservation of the neurovascular bandelettes, which are the erectile nerves that are hugging the prostate.

For all these reasons, it is very important to have a good specialist with experience in the surgical treatment of the prostate in order to guarantee the best possible results and, in the event of a complication, to know how to resolve it in the best possible way.

Until now, only the Da Vinci robot (Intuitive surgical) was available, an excellent device with very good performance and highly developed instrumentation that has helped us to improve the results considerably. In addition, in 2021 the new Hugo robot, from Medtronic, has started to be marketed. We are the first center in Spain, and one of the first in the world, to incorporate it. The Hugo robotic system is very versatile and allows us great surgical flexibility and very versatile surgeries. This acquisition responds to our permanent spirit of searching for excellence and acquiring experience that enriches us when it comes to helping our patients.

When selecting the surgical approach, the most important thing is the experience of the surgeon who is going to operate on us. A good open, laparoscopic and robotic surgeon can obtain very similar results, although it is true that the robot is a very good tool to improve results in most surgeons.

It has been demonstrated that surgeons with more experience and who work in academic institutions obtain much better results. For this reason, I recommend operations with surgeons who have extensive experience and who belong to prestigious institutions and, if possible, who do research, since doing research obliges the professional to collect his results, which is the only way to really know what he is doing and how he can improve.